1. Technical Field
This invention relates to diagnostic imaging, and more particularly to novel contrast agent preparations and their use in diagnostic imaging, for example in visualizing tissue.
2. Prior Art
Imaging technology, including magnetic resonance imaging (MRI), X-ray, positron emission tomography (PET), magnetography, and computed tomography (CT) scanning, has a vital role in the detection and treatment of cancer lesions and other illnesses. For example, MRI technology provides a powerful, non-invasive tool to map and explore the structure and function of soft tissues. In fact, MRI through the use of high-strength magnets and radio-frequency signals can produce three-dimensional images of tissues. Using mechanical imaging system, it is possible to detect neoplastic lesions; the detection of early tumor lesions and metastases still remains challenging.
Contrast agents have been used to improve the intrinsic contrast of the images from imaging technology. This method relies on the administration of contrast agents to amplify the contrast in imaging between the pathological tissue and the normal tissue. The most widely used class of MRI contrast agents are based on gadolinium ion (Gd3+), manganese ion (Mn2+), and iron ion (Fe3+) chelates that are strictly extracellular low molecular weight compounds with T1 reflexivity such as diethylenetriaminepentaacetate (DTPA). Ultimately, the efficacy of a contrast agent depends on both the inherent capability to improve images and the pharmacokinetics.
For example, the Gd3+ based contrast agents approved for clinical use are mainly non-specific small molecules. Such Gd3+ contrast agents usually have relaxivities of <10 mM−1s−1 which are 20 to 50 fold lower than the predicted values. The relaxivities are mainly limited by the rotational correlation time of the molecule. The most commonly used contrast agent, DTPA, has a R1 relaxivity of 5 mM−1s−1. With this relaxivity, a robust clinical examination usually requires a large dose (>0.1 mM local concentration) in order to reach sufficient contrast or to produce an acceptable image. In addition, this class of contrast agents has a very short circulation time that limits the time window for data collection. Efforts to improve such contrast agents have included the covalent or the non-covalent linkage of the small Gd agent to the macromolecules, such as dendrimers or copolymers.
Accordingly, there is always a need for improved contrast agents with higher capabilities to enhance imaging signals. There also is a need for novel protein-based MRI contrast agents with wide applicability in molecular imaging of various tissues, tumors, cancers, and diseases. There also a need for contrast agents that can be retained longer in tissue and blood vessels, especially in that of animals and humans. There also is a need for contrast agents in which the chelating site may be tailored for specific applications and the imaging techniques. It is to these needs among others that this invention is directed.